Device for cleaning pipette probes or stirrers

ABSTRACT

The invention concerns a device for cleaning pipette needles or stirrers, the device comprising a trough which holds cleaning fluid and whose lower region has a fluid duct for filling and/or emptying purposes and whose upper region has at least one feed pipe which leads into at least one nozzle directed into the trough interior. Advantageously, the device has a cylindrical trough and in insert with nozzles which is screwed into the trough. The invention further concerns a method of cleaning pipette needles or stirrers, the material to be washed being introduced into the trough interior and sprayed with a washing fluid. The device can also be sued to flush the interior of a pipette needle.

[0001] The present invention is used in the field of automated analysiswhere liquids are pipetted with pipettes and fluids are stirred withstirrers as necessary.

[0002] The present invention provides a device for cleaning pipetteprobes or stirrers, comprising

[0003] a cavity that holds cleaning fluid and whose lower region has afluid duct for filling and/or emptying the cavity, and

[0004] at least one inlet tube which empties into at least one nozzledirected toward the interior of the cavity.

[0005] When sample fluids such as blood or urine are analyzed, they mustbe pipetted into containers along with any necessary wash fluids,reagents, etc. The pipette must be rinsed between pipettings to avoidcarryover between consecutive samples or reagents. If fluids must bemixed in automated analyzers, this is usually performed using stirrersthat are lowered into the sample fluid. The stirrer must be cleanedbetween each step in the mixing procedure to avoid carryover of thematerial to be mixed by the stirrer. Examples of materials to be mixedinclude fluids and suspensions, such as magnetic microparticles influid.

[0006] Washing device for pipettes and stirrers are known from the priorart in which the devices to be washed are inserted into a cavity filledwith wash fluid and the wash fluid is replaced after one or more washsteps. The fluid is usually replaced by removing the fluid through afluid duct using suction.

[0007] A device for washing pipettes is described in European patentapplication 0 661 542 in which the pipette is inserted into a tube thatsurrounds the pipette at a distance of 1 mm or less. Fluid is injectedinto the tube to wash the pipette.

[0008] Devices with a cavity known in the prior art have thedisadvantage in that the fluid is injected into and emptied from thecavity through the same fluid duct, making it inevitable that used andfresh wash fluid are mixed. Moreover, these devices have thedisadvantage that they operate according to a dilution principle. Inother words, the fluid that adheres to the pipette is diluted with thewash fluid. Even after the pipette is removed from the cavity.therefore, fluid which is contaminated to a certain extent is stilladhered to it. Although this problem is avoided with the devicedescribed in EP-A-0 661 542, this device is limited to a certain type ofpipette because the duct is designed to accommodate a pipette of acertain diameter. This wash device therefore cannot be used withdifferent types of pipettes or for pipettes and stirrersinterchangeably.

[0009] The task of the present invention was to provide a device forcleaning pipettes or stirrers very effectively that can be used to cleanvarious objects such as different types of pipettes or stirrers. Afurther task of the invention was to provide a device with a simplemechanical design that can be integrated into existing automatedanalyzers or automated analyzer concepts.

[0010] A device for cleaning pipettes and stirrers provided by theinvention has a cavity for holding cleaning fluid. The cavity ispreferably shaped like a hollow cylinder with an internal diameter ofbetween 0.7 and 3.5 cm. The cylinder can also have a base that is notround. The area of the cylinder that is filled with wash fluid is about10 cm high, although it can vary up or down considerably, depending onthe application. The cavity can be manufactured from a number ofmaterials such as metals or plastics, with plastics being the preferredmaterial. The device is preferably designed so that it can be securelyattached to a base in an upright position. Moreover, the device has anumber of openings.

[0011] The lower region of the cavity has an opening that serves as afluid duct for filling and/or emptying the cavity. This opening ispreferably located at the lowest point possible inside the cavity toensure that used wash fluid can be removed from the cavity as completelyas possible. This can be accomplished, for instance, if the bottom ofthe cavity is bent or slanted.

[0012] The upper region of the cavity has one or more openings for fluidducts that empty into one or more nozzles. The one or more nozzles aredirected toward the interior of the cavity and serve to spray a pipetteprobe or stirrer that is inserted into the cavity. Each of the nozzlesis preferably positioned so that the fluid stream ejected from it pointsdownward at a 20 to 70°—and preferably approximately 45°—angle fromhorizontal. If the device contains numerous nozzles, it is alsoadvantageous for them to be positioned in such a way that the fluidstreams meet at one point, preferably in the longitudinal axis of thecavity. In an especially preferred design, the nozzles are located in aninsert that can be screwed into the cavity. A groove runs around theoutside of the metal insert that contains holes for the nozzles. Whenthe metal insert is screwed into the cavity, an intermediate space formsin the groove between the cavity and the insert that is filled with washfluid through one or more inlet tubes. In an advantageous design, twoinlet tubes are used that are positioned on opposite sides of thecavity. The insert that is screwed into the cavity can be manufacturedfrom a number of materials such as plastics or metals. Metals arepreferred, especially stainless steels such as 1.4435 and 1.4305 (olddesignations: V2A and V4A), that are resistant to cleaning fluids.

[0013] It is also advantageous to the function of the device provided bythe invention if the upper region of the cavity contains at least oneadditional opening for another fluid duct, below the nozzles. The cavitycan be filled With fresh wash fluid through this fluid duct. This fluidduct can also be used as an outlet for overflowing liquid or to emptyfluids using suction to keep the column of water in the cavity at adefined level. This is especially advantageous if the fluid leaving thenozzles cannot be controlled exactly and the fluid level can thereforenot be controlled simply by any other means. It is advantageous to knowthe fluid level in the cavity in advance to eliminate the need toperform liquid level detection, and to avoid inserting the pipette intothe fluid farther than desired. This also makes it easier to standardizethe wash processes.

[0014] The invention also provides a system consisting of a pipetteprobe attached to a drive arm or a stirrer attached to a drive arm, anda device for cleaning pipette probes or stirrers according to theinvention. “Item to be bashed” in the context of this application refersto both pipette probes and stirrers. Pipette probes or stirrers attachedto a drive arm are commonplace in automated analyzers described in theprior art, so drive arms and their control mechanisms will not bedescribed here in detail. For the present invention, however, it isimportant that a central control unit be provided that coordinates andregulates the movement of the drive arms and the control of the fluidstreams and pumps. The drive arm must move the pipette probe or thestirrer over the opening in the cavity and lower the item to be washedinto the cavity. The drive arm must therefore be capable of performing arotational and translational movement in the vertical planes ortranslational movements in at least two spacial directions.

[0015] The invention also provides a method for cleaning pipette probesor stirrers using a device according to the invention in which thepipette probe or stirrer is inserted into the cavity and sprayed withwash fluid by at least one nozzle. It is favorable to lift the item tobe washed to a height at which the area that is wetted with fluid duringpipetting or stirring is located entirely below the level of thenozzles. On the other hand, it is unfavorable if an area of the item tobe washed is sprayed that is larger than the one described above,because there is a risk of fluid being sprayed on electrical contacts orthe like, or of decreasing the effectiveness of the washing procedure.It is especially favorable if the upper edge of the area of the item tobe washed described above is located 5 to 15 mm below the level of thenozzle. It is advantageous for the spraying to take place while the itemto be washed is lifted out of the cavity. The item to be washed can alsobe inserted into a wash fluid contained in the cavity. The purpose is tosoften any deposits or caked-on substances from the item to be washedand remove them by spraying them with fluid from the nozzles. The itemto be washed is cleaned with fresh wash fluid in the spraying step inorder to prevent contaminating wash fluid from adhering to the surfaceof the item to be washed after the cleaning process is over. As aresult, the wash station fills with this wash fluid. When cleaningpipette probes, it is also an advantage to rinse the inside of theprobes in such a way that the probe is dipped into the wash fluid in thecavity and wash fluid is directed through it. Dipping the pipette probeinto the wash fluid prevents the formation of an aerosol and evenfacilitates cleaning by causing fluid to swirl on the outside of theprobe.

[0016] It is advantageous for the pipette probe to be dipped into thewash fluid in the cavity and removed at a speed of less than 14 cm/secto ensure that all fluid covering the probe falls off without formingdroplets. Once the pipette probe has left the fluid it can be moved at ahigher rate of speed.

[0017] The processes for washing a pipette probe described above applyto both the inside and outside of the probe. It is also possible, ofcourse, to wash just the inside or outside of the probe. It isespecially advantageous to rinse the outside of the pipette between theindividual uptake steps when drawing up two or more different fluidsinto the same pipette probe in order to prevent or at least reducecarryover. This is especially advantageous when analytical tests areperformed with reagents that can also be detected as analytes. In a caselike this, the reagent could be carried over from the first test intothe sample and then lead to a false-positive test result in a subsequenttest of this sample. When drawing up various fluids into one pipetteprobe, it has proven effective to draw up a separating fluid or aseparating air bubble into the pipette probe after drawing up a fluid(e.g., reagent) and only then to draw up another fluid (e.g., reagent orsample).

[0018] Wash fluids (also called cleaning fluids) according to theinvention refer to the fluids and mixtures commonly used with automatedanalyzers, e.g., aqueous solutions to which detergents, salts,preservatives, and possibly solubilizers have been added.

[0019] A device according to the invention is described in greaterdetail using the figures below.

[0020]FIG. 1: Cross section of a device for cleaning pipetteprobes/stirrers

[0021]FIG. 2: Outside view of the device

[0022]FIG. 3: Cleaning steps for a pipette probe

[0023]FIG. 4: Cleaning steps for a stirrer

[0024]FIG. 1 shows a cross section parallel to the longitudinal axis ofthe cleaning device according to the invention. The device (1) has aplatform (2) on the bottom with which the device can be attached to aground plate. The device is manufactured via injection molding with PPS(polyphenylene sulfide). The inside of the device is cylindrical inshape and an initial fluid duct enters the device through the bottom ofthe cylinder. A screw (4) is located on the outside of the device, oneend of which is screwed into the device and the other end of which isoutfitted with a connection for a tube.

[0025] The upper region of the device has two openings on opposite sidesof the device into which flanges (5) are screwed. Tubes (6) that carrywash fluid are located inside the flanges (5).

[0026] The upper end of the device also has internal threads (7) intowhich the steel insert (20) is screwed. Accordingly, the insert (20) hasexternal threads (21) in its lower region. A ring-shaped groove (22) islocated on the outside of the insert above this thread, and runs all theway around the circumference. Together with the device (1), the groove(22) forms a duct for the wash fluid ejected through the tubes (6). Thegroove (22) contains holes (23) that serve as nozzles. The device shownin FIG. 1 has six of these holes (23) that are positioned so that thefluid ejected through them meets the cylindrical axis (11) formed by thedevice. The fluid ejected through the nozzles points downward at a 45°angle from horizontal. The device has two gaskets (24, 25) to seal offthe fluid duct located between the device and the insert (20).

[0027] The device shown in FIG. 1 also has two openings (8) on oppositesides of the device that are located below the nozzles (23) but abovethe opening (3). Screws (9) are screwed into these openings andconnected to tubes (10). The tubes (10) are connected to a suctiondevice (not shown) to ensure that the fluid level in the cavity does notrise above the level of the openings (8).

[0028]FIG. 2 shows a side view of the cleaning device according to theinvention. The device (1) and screws (4, 6, and 9) are clearly visiblein this drawing. The insert (20) that is screwed into the deviceprojects out of the top of the device. The upper edge of the insert hasa flange (26) with a rough-milled surface that facilitates handling whenscrewing or unscrewing the insert (20). A device according to theinvention with an insert screwed into place has the advantage that it iseasier to clean when the insert is removed.

[0029]FIG. 3 shows the cleaning steps for a pipette probe, also called adispensing probe. In step (a), the dispensing probe is moved over thecleaning device according to the invention (labelled WD1 in the figure).At this point, fluid from the previous cleaning cycle is already locatedin the cavity of the cleaning device. In step (b), the pipetting probe(labelled DN) is lowered to the surface of the liquid using electronicliquid level detection (LLD). In step (c), the fill level detected withliquid level detection is checked. The fluid column is then lowered inthe cavity (step (d)) and the pipette probe is lowered to the fluidcolumn, which is now lower (step (e)). Using this procedure, theinjecting and emptying function of the system can be checked, and thepresence of fluid in the cavity can be monitored. The fluid column islowered completely in step (f) and the pipette probe is lowered into thecleaning device to the point where the probe tip enters a tapered regionof the cleaning device (see step (g)). The inside of the pipette probeis now flushed with fresh wash fluid. Since the pipette tip ispositioned in the low, tapered region and fluid is removed through thefluid duct on the bottom at this point, the wash fluid exiting thecleaning device is prevented from forming an aerosol, and the upperregion of the wash station is prevented from being contaminated withthis wash fluid.

[0030] After this internal wash step, the pipette is positioned as shownin step (h) so that the pipette tip is washed with the confluence ofwash fluid streams. The pipette can be located above or below thesurface of the column of wash fluid at this point. The cavity fills withwash fluid when the dispensing probe is sprayed. After washing, thepipette is inserted slightly into the wash fluid (see step (i)). Thisposition can be identical to the position in which fluid falls off ofthe probe. The interior of the pipette is now rinsed again when fluid isinjected through it into the cavity (see step (i)). After this rinsestep, the pipette is moved into a defined position in which fluid fallsoff of the probe k), if necessary. The pipette is then slowly removedfrom the wash fluid (step (k)). After the pipette is removed from thecleaning device, it returns to its home position (see step (l)).

[0031] If substance to be dispensed is located in the dispensing probe,only the exterior of the probe is rinsed. This cycle begins with thehome position (a), skips steps (b) through (g) and continues with (h).The rinsing takes place as described in (h) (the cavity is still filledas shown in (a)). Step (i) is skipped, and the cycle ends with steps(j), (k), and (l). In this procedure, it is advantageous for a smallquantity of fluid and/or an air bubble to be drawn up at the end orafter step (h). It is especially favorable if fluid is drawn into thedispensing probe from a drop that remains on the tip of the dispensingprobe after spraying. It is also possible to draw fluid up immediatelyfrom the clean surface of the fluid in the wash station.

[0032] An air bubble is drawn up at the end of step (k) or (l). Thisquantity of fluid, which serves as a separator, is usually less than 5μl, and is preferably between 1 and 3 μl. The fluid is preferably drawnup only after a reagent drawing up and before a sample drawing up. Thesame sequence applies for drawing up an air bubble.

[0033]FIG. 4 shows the cleaning steps for a stirrer. The home positionof the cleaning device with the stirrer is shown in FIG. 4a. A watercolumn is formed and the stirrer is dipped into the wash fluid (FIG. 4b,c, and d). The stirrer is cleaned by turning it, the column of water islowered (FIG. 4e). The stirrer is rotated quickly to spin off any fluidstill adhering to it (FIG. 4f). The stirrer is then removed from thecleaning device. Legend  1 Device  2 Platform  3 Fluid duct  4 Screw  5Screw  6 Tube  7 Internal thread  8 Hole  9 Screw 10 Tube 20 Insert 21External thread 22 Ring-shaped groove 23 Bore holes 24, 25 Gaskets 26Rough-milled flange

1. Device for cleaning pipette probes or stirrers with a cavity forholding cleaning fluid that has a fluid duct in its lower region forfilling and/or emptying the cavity, and at least one inlet tube in itsupper region that is connected to at least one nozzle that is directedtoward the interior of the cavity.
 2. Device according to claim 1 with apipette probe or a stirrer that is attached to a transport arm. 3.Device according to claim 1 that has at least one discharge duct thatenters the interior of the cavity above the fluid duct and below theinlet tube.
 4. Device according to claim 1 in which the cavity isbasically cylindrical in shape.
 5. Device according to claim 1 in whichthe at least one inlet tube empties into a duct that has numerousnozzles on the side facing the interior of the cavity.
 6. Deviceaccording to claim 5 in which the nozzles are basically positioned atthe same height and are directed towards the longitudinal axis (11) ofthe cavity.
 7. Device according to claim 5 or 6 with two inlet tubessituated on opposite sides.
 8. Device according to claim 5 or 6 with acylindrical metal insert that has a groove around its circumference thatforms a channel in cooperation with the interior wall of the cavity andinto which the at least one inlet tube empties.
 9. Device according toclaim 1 in which the bottom of the cavity is slanted or bent, and thefluid duct for filling and/or emptying the cavity opens into the lowestlevel of the cavity.
 10. Device according to claim 1 with at least oneadditional fluid duct that empties into the interior of the cavity belowthe at least one inlet tube and above the fluid duct in the lowerregion, and through which fluid is injected into the interior of thecavity or drawn out of the cavity.
 11. Method for cleaning pipetteprobes or stirrers with an apparatus according to claim 1 in which apipette probe or stirrer is inserted into the interior of the cavity andthen sprayed with a wash fluid ejected through at least one nozzle. 12.Method according to claim 11 in which the pipette probe or stirrer isalso inserted into a wash fluid contained in the cavity.
 13. Methodaccording to claim 12 in which the pipette probe or stirrer is insertedinto the wash fluid contained in the cavity and then removed with aspeed slower than 14 cm/sec.
 14. Method according to claim 12 in whichwash fluid is lead through the pipette probe while it is immersed in thewash fluid in order to wash the interior of the probe.
 15. Method forcleaning pipette probes according to claim 11 in which fluid is locatedin the pipette probe before the spraying step, and a separating fluidand/or air bubble is drawn into the pipette probe before or after thespraying step.
 16. Method according to claim 15 in which the separatingfluid is drawn up during the spraying step or in which the separatingfluid is drawn from a droplet that remains on the pipette probe afterthe spraying step, or that is drawn from the cavity before or after thespraying step.
 17. Method according to claim 15 or 16 in which less than5 μl, and preferably 1 to 3 μl of separating fluid and/or an air bubbleof the respective volume is drawn up.
 18. Method according to claims 15to 17 in which another fluid is drawn into the pipette probe after theseparating fluid.
 19. System comprising a pipette probe attached to adrive arm or a stirrer attached to a drive arm, and a cavity for holdingfluid that has a fluid duct in its lower region for filling and/oremptying the cavity, and at least one inlet tube in its lower regionthat empties into at least one nozzle that is directed towards theinterior of the cavity.
 20. System according to claim 14 that also has apump that serves to fill and/or empty the cavity and to supply the inlettube with fluid, and a central control unit that coordinates andcontrols the at least one pump and the movement of the drive arm.